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Cutaneous Vasculitides - Clinical Manifestations, Diagnosis, and Aetiology

Calciphylaxis and the arteriolosclerotic ulcer of Martorell (ASUM) represent two entities of cutaneous calcific arteriolopathies. Their differential diagnosis can be challenging, given similarities in their clinical and histological presentation. Calcification patterns have been proposed as a possible discriminative histological criterion, however, a systematic microstructural comparative analysis is lacking.The study aimed at a systematic comparative microstructural analysis of the calcification patterns in calciphylaxis versus ASUM.Skin biopsies of patients with leg ulcers due to calciphylaxis (20) and ASUM (69) diagnosed at three European wound care centres (Vienna, Bern, Zurich) were included. The extent of calcification, arteriolar calcification pattern and presence of extra-arteriolar calcification were assessed.All calciphylaxis and most ASUM patients (77%) presented with arteriolar calcification. Although the mean number of calcified vessels and the proportion of calcified area were significantly higher in calciphylaxis specimens (p = 0.003 and p = 0.0171), there was no significant difference in the pattern of arteriolar calcification (p = 0.177). Interestingly, extra-arteriolar calcification was detected in the majority of both calciphylaxis (93.3%) and ASUM samples (85.2%, p = 0.639). Notably, Alizarin Red S staining was superior to HE for the detection of calcifications of both entities (p = 0.014 and p 0.0001), and to von Kossa staining for ASUM samples (p = 0.0001). However, no differences could be observed between cases with uraemic and non-uraemic calciphylaxis or ulcerations located on the upper and lower leg.Our results indicate that extra-arteriolar calcification is not only present in calciphylaxis, but can also be detected in ASUM suggesting a lack of specificity for this finding. However, more specific calcification stains, such as Alizarin Red S, should be used in suspected cases, as calcifications may be overlooked using conventional HE staining.

BACKGROUND Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids. OBJECTIVE To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS. STUDY DESIGN Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12��weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters. RESULTS Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate. At 12��weeks, the mean clinical LS scores improved from 4.6 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p��=��0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, p��=��0.095). LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol 0.35; 95% CI 0.06 to 2.06, p��=��0.234). No drug-related serious adverse event occurred during the trial. CONCLUSIONS Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12��weeks treatment.

Background Moulages can greatly extend the possibilities of simulation in teaching and assessment. Since moulages that fit an educator’s exact needs are often unavailable commercially, this paper explains how 2-dimensional transfer tattoos can be independently developed, produced, and evaluated. Methods From representative photographs of the specific skin condition an analogue copy of the pathological finding is drawn. Once validated by the medical expert, it can be digitized by scanning and processed using graphics software. The final digital image file is printed onto transfer paper. Once applied and fixed onto the intended wearer, usually a simulated patient, its authenticity can be confirmed, and further transfer tattoos can be produced. Results Using this moulage technique we produced 10 different 2-dimensional transfer tattoos to date, including hematoma, Janeway lesions and splinter nails. These moulages are used in clinical skills training, formative and high-stakes summative assessment in undergraduate medical and nursing programs. Conclusions By sharing our development process for 2-dimensional transfer tattoos, health profession educators can produce their own that best fit their local educational needs. Due to their high authenticity and standardization, 2-dimensional transfer tattoos are ideal for use in high-stakes assessment.

Background: Multiple studies have compared the performance of artificial intelligence (AI)–based models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice. Objective: The objective of the study was to systematically analyse the current state of research on reader studies involving melanoma and to assess their potential clinical relevance by evaluating three main aspects: test set characteristics (holdout/out-of-distribution data set, composition), test setting (experimental/clinical, inclusion of metadata) and representativeness of participating clinicians. Methods: PubMed, Medline and ScienceDirect were screened for peer-reviewed studies published between 2017 and 2021 and dealing with AI-based skin cancer classification involving melanoma. The search terms skin cancer classification, deep learning, convolutional neural network (CNN), melanoma (detection), digital biomarkers, histopathology and whole slide imaging were combined. Based on the search results, only studies that considered direct comparison of AI results with clinicians and had a diagnostic classification as their main objective were included. Results: A total of 19 reader studies fulfilled the inclusion criteria. Of these, 11 CNN-based approaches addressed the classification of dermoscopic images; 6 concentrated on the classification of clinical images, whereas 2 dermatopathological studies utilised digitised histopathological whole slide images. Conclusions: All 19 included studies demonstrated superior or at least equivalent performance of CNN-based classifiers compared with clinicians. However, almost all studies were conducted in highly artificial settings based exclusively on single images of the suspicious lesions. Moreover, test sets mainly consisted of holdout images and did not represent the full range of patient populations and melanoma subtypes encountered in clinical practice. info:eu-repo/semantics/publishedVersion

Background: Prurigo pigmentosa (PP) is an inflammatory dermatosis typically reported in young Asian women and characterized by recurrent papulovesicular lesions resolving with a postinflammatory reticulated hyperpigmentation. Methods: We have included all consecutive patients with PP diagnosed in our tertiary center between 2013 and 2020. The clinical information was retrospectively collected from medical records. Results: We identified 14 patients with PP. The median age at the time of diagnosis was 29.5 years (range 17–43 years), while the female-to-male ratio was 13:1. Diagnostic delay varied from 10 days to 10 years (mean of 25 months). Light microscopy studies consistently showed presence of a lymphohistiocytic infiltrate in combination in 40% of cases with neutrophils. Interface changes were found in 60% of cases. In 6 (43%) of 14 cases, there was a chronological relationship between the starting of a new diet and the development of the first flares. Treatment with doxycycline in 9 patients resulted in a complete regression of the lesions. Limitation: This was a retrospective study in a tertiary referral hospital. Conclusions: Our observations indicate that PP is not so rare in Europe as previously thought and is often diagnosed after a long delay. Demographics, clinical characteristics and triggering factors in Caucasian patients are similar to those described in the Asian population. Diagnosis is based on the peculiar recurrent course and distinctive clinicopathological features. Tetracyclines represent the first-line therapy in PP.

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Background: There are no proper management guidelines for nail apparatus melanoma (NAM). Objective: This study aimed to describe the clinical features, the presence of locoregional and distant metastases and disease-free and overall survival of NAM treated at our institution. Methods: A retrospective cohort review of patients with single, primary localized histopathologically confirmed NAM was performed. Collected data consisted of patients’ characteristics and tumor features. In addition, local recurrence, locoregional metastases, distant metastases, disease-free survival (DFS) and overall survival (OS) were used as the main outcomes in our analysis. Results: Thirty patients with NAM were included. The overall survival (OS) in our patients at 5 and 10 years was 85.6 and 73.4%, respectively. DFS was significantly higher in patients with primary tumor location in the hand and without tumor-infiltrating lymphocytes (p value = 0.01 and 0.04, respectively). The patients with in situ melanoma or Breslow thickness Conclusion: Primary tumor location in the hand and lower tumor thickness might be correlated with better patients’ survival. The study results suggest that total amputation might not be necessary in all NAM cases.

Journal of the American Academy of Dermatology : JAAD 86(3), 640-642 (2022). doi:10.1016/j.jaad.2021.02.009, Published by Elsevier, Amsterdam [u.a.]

International audience; Skin involvement in Waldenström's macroglobulinaemia is poorly described, and diagnosis of this disorder may be difficult. Many differential diagnoses are possible (other lymphomas, primary cutaneous lymphoma, etc.). Describing 2 aspects of Waldenström's macroglobulinaemia (infiltration by lymphoplasmacytic tumour cells or histological transformation into diffuse large B-cell lymphoma) allows the identification of clinical, histological and immunohistochemical diagnostic aids. Detection of the MYD88 L265P mutation is of interest. This study identified a characteristic clinical picture in non-transformed cases, and was able to distinguish between transformed and non-transformed cases by their severity and poor prognosis. Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the followup of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).

In the oral mucosa, a precise classification of inflammatory lesions with a histopathological lichenoid inflammation represents a diagnostic challenge. Oral lichen planus (OLP) and oral lichenoid lesions (OLL) share several clinical and histopathological characteristics, therefore it is often difficult to distinguish between them. However, considering that the pathophysiologic mechanisms and the treatment approach of OLP and OLL are different, an early distinction of between these two diseases is meaningful.

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Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive antitumor activity. However, it causes adverse effects, including lichenoid reactions. Cases of ICI-triggered bullous pemphigoid (BP) and anecdotally mucous membrane pemphigoid (MMP) have also been reported. We describe two new cases of pembrolizumab-triggered MMP, one of which was associated with cutaneous lichenoid lesions.

Clinical differential diagnosis of arteriolosclerotic ulcers of Martorell is challenging due to the lack of clearly affirmative instrument-based diagnostic criteria. The aim of this study was to develop vascular histomorphological diagnostic criteria differentiating Martorell ulcers from other types of leg ulcers. The histomorphology of patients diagnosed with arteriolosclerotic ulcers of Martorell (n���=���67) was compared with that of patients with venous leg ulcers, necrotizing leukocytoclastic vasculitis, pyoderma gangrenosum, and non-ulcerative controls (n���=���15 each). In a multivariable logistic regression model, the rates of arteriolar calcification (odds ratio (OR) 42.71, 95% confidence interval (CI) 7.43-443.96, p���

BACKGROUND Direct immunofluorescence microscopy (DIF) studies constitute the gold standard for diagnosis of bullous pemphigoid (BP) but depend on the availability of specialized laboratories and often on an additional skin biopsy specimen. OBJECTIVES To assess the value of immunohistochemical analyses (IHCA) in the diagnosis of BP using formalin-fixed, paraffin-embedded skin biopsy specimens as an alternative to DIF; and to study the correlation between the results of IHCA and the presence of histological subepidermal blister formation and of circulating autoantibodies by indirect immunofluorescence studies using split skin or by enzyme-linked immunosorbent assays. METHODS We included all patients newly diagnosed with BP evaluated between 2008 and 2010. There were 51 consecutive skin biopsy specimens obtained from 38 patients with BP with positive DIF. RESULTS By IHCA, deposits of immunoreactants were found in 45% of all tested cases. Deposits of C3d, IgG, IgM, IgE and IgA were found in 37%, 23%, 2%, 0% and 0% of cases, respectively. Deposits of C3d and/or IgG were found in 79% of the 24 cases with a blister and in 83% of the 12 cases with subepidermal blistering and positive immunoserological analyses, respectively. CONCLUSIONS In contrast to previous studies, our findings in an unselected patient cohort indicate that IHCA are not sufficiently sensitive to replace DIF studies for confirming the diagnosis of BP. IHCA sensitivity significantly increases in the presence of histological blistering and/or of circulating autoantibodies. IHCA represents a potential rescue diagnostic technique only if specialized laboratories and/or a second biopsy specimen for DIF are unavailable.

BACKGROUND Bowen disease is the most frequent nail malignancy, usually seen as a verrucous plaque of the nail in men. OBJECTIVE To characterize the affected patient population, the clinical manifestations, the diagnostic delay and diagnostic steps, and presence of human papilloma virus (HPV) infection. METHODS We retrospectively evaluated all cases of Bowen disease of the nail unit over a period of 9 years. Data were obtained from our electronic database. Human papilloma virus genotype was assessed in biopsy specimens by polymerase chain reaction (PCR) sequencing. RESULTS We identified 12 cases of Bowen disease of the nail unit in 10 patients. Mean age at onset was 52 years, with a male predominance of 90%. The thumb and middle finger were the most frequently affected (66%). Fifty percent of the lesions presented as periungual and subungual verrucous tumours. Patients sought medical evaluation after a mean delay of 5.7 years; histopathological diagnosis was made after a mean delay of 3.2 years. HPV infection was identified in 75% of the cases. CONCLUSIONS Any recently appeared verrucous lesion of the nail unit in men above the age of 40 years should raise the suspicion of Bowen disease and lead to further histopathological diagnostic procedures.

The histopathological differentiation of melanocytic nevi from malignant melanoma (MM) is based on well-known criteria, and is straightforward in the vast majority of cases. However, there are few cases of melanocytic lesions (ML), the diagnosis of which is very challenging or even impossible. Here we have studied several morphological characteristics with particular focus on elastic fibers (EF) to identify features, helpful for the distinction between nevi and MM. In a monocentric retrospective study we have analyzed 14 morphological histological characteristics in 30 MMs and 90 nevi, encompassing 30 compound/dermal nevi, 30 junctional nevi, 30 dysplastic nevi. All consecutive cases were retrieved from the archives of our tertiary referral centre during the 6-month study period. Nine characteristics including loss of EF in the ML, loss of EF in lesional fibrosis, pushing of the EF, UV-elastosis, loss of rete ridges of the epidermis, regression of the ML, atrophy of the epidermis, pigment incontinence, and concentric eosinophilic fibroplasia (CEF) showed a statistical significant difference (p 2) distinguishing nevi from MM. Loss of EF was found in 73.1% of MM cases, but in less than 2.5% of nevi. We identified nine morphological characteristics that are helpful to differentiate melanocytic nevi from MM. A loss of the EF in a ML appeared to be highly associated with MM.

Eosinophil infiltration can be observed in skin disorders, such as allergic/immunologic, autoimmune, infectious, and neoplastic diseases. Clinical presentations are variable and include eczematous, papular, urticarial, bullous, nodular, and fibrotic lesions; pruritus is a common symptom in all. In this review, we present representative eosinophilic skin diseases according to their clinical pattern, together with histologic findings and diagnostic procedures. We also discuss the potential roles of eosinophils in the pathogenesis of dermatologic disorder. Current pathogenesis-based diagnostic and therapeutic approaches are outlined.

Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male-female ratio, 7:5; median age, 61 years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma such as Sezary syndrome or CD30+ T-cell lymphoproliferative disorder. All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs associated with fever. All but one had received a polychemotherapy for an acute myeloid leukemia (n=10) or a urothelial carcinoma (n=1) before the occurrence of the skin eruption. One had an autoimmune lymphoproliferative syndrome causing chronic agranulocytosis requiring granulocyte colony-stimulating factor injection. In all patients, the skin eruption was associated with a slight increase of white blood cell count followed by bone marrow recovery within the next weeks. All skin biopsies showed a dermal perivascular lymphocytic infiltrate containing atypical medium- to large-sized CD3+, CD4+ and CD8+, CD25+, ICOS+, PD1- lymphocytes with a strong CD30 expression in most instances (n=10), suggesting the recruitment of strongly activated T cells in the skin. In 6 patients, a diagnosis of CD30+ lymphoproliferative disorder or Sezary syndrome was proposed or suspected histopathologically, and only the clinical context allowed the diagnosis of ELR with a peculiar presentation with atypical lymphocytes. We describe a series of patients with an unusual form of ELR characterized by the presence of atypical activated T cells in the skin. On a practical ground, pathologists should be aware of this distinctive and misleading presentation.

BACKGROUND Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. METHODS Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-β, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). RESULTS Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. CONCLUSIONS The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is an aggressive primary cutaneous B-cell lymphoma affecting older people.1 Rituximab (RTX) combined with polychemotherapy (RTX-PCT) has improved survival but relapses are frequent.2 Central nervous system (CNS) involvement is rare and poorly described. This article is protected by copyright. All rights reserved.

Introduction Finding new markers to assess prognosis of melanoma without the necessity to perform a surgical interventions is an important goal in melanoma research. The current study aimed to assess the correlation of clinical course and prognosis of primary and metastatic melanoma with expression of VEGF family and their receptors. Methods A ngTMA block was made from the randomly selected paraffin tissue blocks of the patients with melanocytic nevi, primary and metastatic melanoma. Then sections cut from ngTMA-block were immunohistochemically stained with proper antibodies. Expression of these proteins was investigated using automated image analysis and compared among the study groups. Results We analyzed the tissue of 238 patients with following diagnoses: 101 (42.4%) with a diagnosis of nevus, 86 (36.1%) Malignant melanoma and 51 (21.4%) metastasis. Median follow-up time for the malignant lesions was 5.71 years. Among the tested antigen, VEGF-C (p = 0.016), VEGF-R2 (p

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

Summary Background Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the skin associated with IgG autoantibodies to BP180 and BP230, while mucous membrane pemphigoid (MMP) comprises a heterogeneous group of autoimmune blistering diseases characterized by a predominant mucous membrane involvement and scarring tendency associated with an autoantibody response to various autoantigens, including BP180. While the pathogenicity of IgG autoantibodies to BP180 has been demonstrated in BP, the role of IgE autoantibodies in mediating tissue damage in BP and MMP is unclear. Objectives To assess the presence of tissue-bound IgE in patients with BP and MMP, and their correlation with distinct clinical features. Methods In this retrospective study, we assessed the presence of IgE deposits as detected by direct immunofluorescence microscopy of skin biopsy specimens obtained from 44 and 13 patients with a new diagnosis of BP and MMP, respectively. Distinct clinical features at time of diagnosis, such as itch, urticarial papules and plaques and eczematous lesions, were noted. Results In 18 of 44 (41%) patients with BP linear deposits of IgE of variable intensity were detectable along the dermoepidermal junction. In 14 (32%) of the cases, IgE deposits were found concomitantly with IgG and C3. In two (5%) patients, diagnosis of BP was based on the isolated detection of IgE together with consistent clinicopathological features. Nine of 13 (69%) patients with MMP also exhibited linear IgE deposits, including one case with isolated linear IgE deposits. Patients with BP with tissue-bound IgE deposits had clinically significant urticarial papules and plaques when compared with patients with BP without IgE deposits. Conclusions Our findings indicate that demonstration of tissue-bound IgE deposits provides an additional useful criterion for diagnosis of BP and MMP in some patients. Prospective studies are needed to better correlate the presence of tissue-bound and circulating IgE autoantibodies and their specificity with distinct clinical features and course of BP and MMP.

Amicrobial pustulosis of the folds (APF) is a recently described entity characterized by relapsing pustular lesions predominantly involving the cutaneous flexures and scalp. This disease typically occurs in association with systemic lupus erythematosus and a variety of other autoimmune diseases. We here describe an APF-like pustular eruption predominantly affecting the scalp, face and trunk, occurring during long-term infliximab treatment for Crohn’s disease. Immunohistochemical staining of skin biopsy specimens for myxovirus resistance protein A, a marker for type 1 interferon-inducible proteins, showed increased staining in the epidermis and dermal mononuclear inflammatory infiltrate. Our observation further extends the spectrum of cutaneous adverse reactions potentially related to anti-tumor necrosis factor-α, the clinical context in which APF can occur as well as its clinical presentations.

Background: Recently, Petrella et al. described four patients with an unusual CD8+ lymphoid proliferation arising on the ear. These cases do not correspond clearly to any recognized category of cutaneous T-cell lymphoma (CTCL) described in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) 2005 classification. Methods and Results: Three patients (all men; median age 64; range: 61-69) presented with plaques or small tumors localized on the ears. All lesions showed histopathologically a dense, diffuse infiltration of lymphocytes within the entire dermis without epidermotropism. Cytomorphology revealed predominance of medium-sized pleomorphic lymphocytes. Immunohistochemistry showed a cytotoxic phenotype (CD3 + /CD4 −/CD8 +). Polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR)-gamma gene revealed a monoclonal rearrangement in two of three patients. Follow-up data of two patients were available; one is alive without skin or systemic manifestations of the disease after 28 months, whereas the other is alive with persistent skin disease after 7 months. Conclusions: Our observation confirms that some patients present with a peculiar lymphoid proliferation of small-medium pleomorphic cytotoxic lymphocytes located on the ear, probably representing a phenotypic variant of the cutaneous small/medium pleomorphic T-cell lymphoma (CSMPTCL). These cases should not be misinterpreted as a high-grade cytotoxic lymphoma.

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.

The treatment of morphoeic (or sclerosing) basal cell carcinoma (mBCC) of the face is associated with high rates of incomplete excision and recurrence. A principal risk factor for incomplete resection is the grade of surgeon. We did a prospective, randomised study of 40 consecutive patients with mBCC of the face. The extent of the tumour was assessed under standard conditions by consultant surgeons and compared with assessments by resident surgeons with the help of the Varioscope, a combination of microscope and loupe glasses with strong illumination and a maximal magnification of 7x. The data from a former retrospective study of all excisions of mBCC of the face during a five-year period at the hospital served as control. Residents with the support of the Varioscope achieved a rate of incomplete excisions similar to that of consultants under standard conditions. There was a significant reduction of the rate of incomplete resections by resident surgeons thanks to high magnification and good lighting (p=0.02). High magnification and good lighting were useful in learning how to recognise skin changes associated with mBCC of the face and achieving a low rate of incomplete excisions.

Objective: To report a case of lichenoid drug eruption (LDE) after starting antihypertensive treatment with nebivolol, a cardioselective β-blocker. Case Summary: Five weeks after starting treatment with nebivolol, a 62-year-old woman presented with erythematous papules on both extremities and skin lesions spreading over the back. She was not being treated with any other drugs. Because the administration of levocetirizine, topical methylprednisolone, and systemic prednisone was unsuccessful, the treatment was stopped and the lesions were biopsied. The histopathological features of the lesions were consistent with LDE. After withdrawal of nebivolol and subsequent readministration of topical methylprednisolone and systemic prednisone, the skin lesions resolved within 12 days. Assessment of the causality revealed a probable relationship between nebivolol and the lichenoid eruptions. Discussion: Although β-blockers can be associated with LDE, as of July 7, 2006, this has not been previously reported with nebivolol. T cells invading the dermis are considered to be responsible for epidermal destruction associated with LDE, as has been described for lichenoid forms of chronic graft versus host disease and idiopathic lichen ruber planus. Conclusions: Nebivolol can cause LDE, as has been reported with other β-blockers. The underlying mechanism appears to be T cell–mediated. Cross-reactivity with other β-blockers cannot be excluded; therefore, the risk of recurrent LDE should be weighed carefully against the clinical benefit before switching to another β-blocker.

Cutaneous drug reactions occur with a frequency of 1-8% and can be higher for certain classes of drugs. They can range from mild morbilliform eruptions to more severe forms such as drug-hypersensitivity syndrome, toxic epidermal necrolysis or anaphylaxis. Acute generalized exanthematous pustulosis (AGEP) is considered to be a clinical reaction pattern, which is induced in over 90% of the cases by systemic drugs. It is a rare presentation of an adverse drug reaction most frequently triggered by anti-infectious drugs. A high proportion of these cases have been attributed to aminopenicillins and macrolides. We report a terbinafine-induced AGEP in a 68-year-old male confirmed by lymphocyte stimulation in vitro, and review the published cases induced by antimycotic drugs with special emphasis on terbinafine-triggered cases.

BACKGROUND Proper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub-Saharan Africa, where little is known about the spectrum of histopathological features observed. OBJECTIVES To investigate the spectrum of dermatopathological diagnoses made in a sub-Saharan African reference centre of a large, mainly rural area. PATIENTS/METHODS To retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania. RESULTS There were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC. CONCLUSIONS In this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.

Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.

Background: Urgent consultations for skin disorders are commonly done in different settings. Scarce data exist about the characteristics of these patients. Objective: The aim of this study was to analyse specific characteristics of patients receiving an urgent consultation at a dermatology department in a university hospital. Methods: We prospectively recorded the data of all patients having had an urgent consultation during a period of 12 months. Results: We registered 2,222 urgent consultations. The most frequent diagnoses were eczemas (24.8%), dermatomycoses (5.1%) and dermatitis not otherwise specified (4.8%). The most frequent treatments were topical steroids, emollients, topical antibiotics, systemic antihistamines, antibiotics and virostatics. 2.2% of patients were hospitalized, 78.8% asked for a consultation for a disease lasting less than 4 weeks, and 6.9% presented the same day as the skin disease appeared. Conclusions: This study shows the characteristics of patients receiving an urgent dermatologic consultation. It underlines the need for collaboration between dermatologists, other physicians, general practitioners and nurses.

BACKGROUND Skin cancer is rare among Africans and albinism is an established risk for skin cancer in this population. Ultraviolet radiation is highest at the equator and African albinos living close to the equator have the highest risk of developing skin cancers. METHODS This was a retrospective study that involved histological review of all specimens with skin cancers from African albinos submitted to The Regional Dermatology Training Center in Moshi, Tanzania from 2002 to 2011. RESULTS A total of 134 biopsies from 86 patients with a male to female ratio of 1:1 were reviewed. Head and neck was the commonest (n = 75, 56.0%) site affected by skin cancers. Squamous cell carcinoma (SCC) was more common than basal cell carcinoma (BCC) with a ratio of 1.2:1. Only one Acral lentiginous melanoma was reported. Majority (55.6%) of SCC were well differentiated while nodular BCC (75%) was the most common type of BCC. CONCLUSIONS Squamous cell carcinoma is more common than basal cell carcinoma in African albinos.

BACKGROUND Neutrophilic dermatoses comprise a wide spectrum of inflammatory diseases with overlapping features characterized histologically by the presence of an aseptic neutrophilic infiltrate in the epidermis, dermis, and/or hypodermis and are often associated with systemic inflammatory and neoplastic disorders. OBSERVATIONS We describe 3 patients with an unusual neutrophilic dermatosis characterized by relapsing episodes of fever, widespread infiltrated plaques with bullous appearance, and variable involvement of the arms, legs, abdomen, and/or trunk. Light microscopy studies showed marked edema of the papillary dermis with an inflammatory infiltrate consisting mainly of mature neutrophils. All 3 patients were morbidly obese, and workup revealed underlying cancer in 2 cases: myeloma and breast carcinoma. Management of the underlying disease resulted in long-term remission of the skin disease. CONCLUSIONS The clinicopathologic features in our 3 cases best correspond to a widespread giant cellulitis-like form of Sweet syndrome. Knowledge of this newly observed unusual variant of Sweet syndrome within the broad spectrum of neutrophilic diseases is important for its prompt and proper management.

Cutaneous reactive angiomatoses (CRA) encompass a distinct group of rare benign reactive vascular proliferations that include reactive angioendotheliomatosis, diffuse dermal angiomatosis and reactive intralymphatic histiocytosis. The etiology of these conditions, often associated with either localized or systemic diseases, is poorly understood. We report a 72-year-old woman who presented giant diffuse cellulitis-like plaques on the right lower limb and the pelvis and a reduction of her general condition with fever. Light microscopy studies revealed combined features of reactive angioendotheliomatosis, diffuse dermal angiomatosis and reactive intralymphatic histiocytosis. A small arteriovenous fistula of the right lower leg was thought to act as trigger. Systemic corticosteroids resulted in the clinical remission of the skin lesions. Our observation provides strong evidence that reactive angioendotheliomatosis, diffuse dermal angiomatosis and reactive intralymphatic histiocytosis, previously regarded as distinct forms of CRA, may show overlapping histopathological features and most likely represent facets of the same disease.

We describe a 60-year-old man with pancreatic panniculitis associated with arthritis and peripheral eosinophilia in whom the skin symptoms led to a diagnosis of an underlying acinar cell cystadenocarcinoma. The panniculitis involved initially the legs, but soon thereafter lesions developed on the trunk and upper extremities. In the literature, only 5 cases of pancreatic acinar cell cystadenocarcinoma have been reported, none of these in association with panniculitis.

Background: In autologous cell therapy, e.g. in melanocyte transplantation for vitiligo, a minimally invasive mode of transepidermal delivery of the isolated cells is of crucial importance to reduce potential side effects such as infections and scarring as well as to minimize the duration of sick leave. Objectives:To compare the characteristics of the microscopic treatment zones induced by ablative fractional CO2 laser and by microneedle treatment in ex vivo human breast skin. Results: Ablative fractional CO2 laser treatment resulted in superficial, mainly epidermal defects reaching at most the upper papillary dermis (0.1–0.3 mm), covered by a thin eschar and coated by a small zone of collagen denaturation. Tissue injury characteristics depended on spot size as well as the energy delivered. Microneedle treatment led to thin vertical skin fissures, reaching the middermis (up to 0.5 mm) and injuring dermal blood vessels, but without surrounding tissue necrosis. Conclusions: Both technologies are able to create small epidermal defects which allow to deliver isolated cells such as melanocytes to an epidermodermal site, with microneedle treatment having the advantage of lacking devitalized tissue and eventually enabling vascular access for the transplanted cells.

Background Cutaneous T-cell lymphoma can be associated with clinically significant nail alterations, the presentation of which can be protean and misleading. To date, only a few reports have demonstrated direct specific tumor infiltration of the nail bed, while little is known about the efficacy of topical treatments. Observations We describe the case of a 93-year-old man presenting with Sezary syndrome who developed clinically significant nail alterations. Light microscopy studies and T-cell receptor rearrangement analysis demonstrated the presence of a specific lymphocytic infiltrate within the nail bed. The patient was given repeated courses of topical mechlorethamine, leading to a sustained complete remission of both skin and nail alterations. Conclusions Specific nail involvement should be recognized and considered in all patients with cutaneous T-cell lymphomas. Topical mechlorethamine remains an attractive therapeutic option in cases of specific nail alterations, especially for situations in which systemic therapies are either not indicated or unlikely to be well tolerated.

Patients with skin nodules characterized by the infiltrate of pleomorphic small/medium T lymphocytes are currently classified as "primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma" (SMPTCL) or as T-cell pseudolymphoma. The distinction is often arbitrary, and patients with similar clinicopathologic features have been included in both groups. We studied 136 patients (male:female = 1:1; median age: 53 years, age range: 3-90 years) with cutaneous lesions that could be classified as small-/medium-sized pleomorphic T-cell lymphoma according to current diagnostic criteria. All but 3 patients presented with solitary nodules located mostly on the head and neck area (75%). Histopathologic features were characterized by nonepidermotropic, nodular, or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. A monoclonal rearrangement of the T-cell receptor-gamma gene was found in 60% of tested cases. Follow-up data available for 45 patients revealed that 41 of them were alive without lymphoma after a median time of 63 months (range: 1-357 months), whereas 4 were alive with cutaneous disease (range: 2-16 months). The incongruity between the indolent clinical course and the worrying histopathologic and molecular features poses difficulties in classifying these cases unambiguously as benign or malignant, and it may be better to refer to them with a descriptive term such as "cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance," rather than forcing them into one or the other category. On the other hand, irrespective of the name given to these equivocal cutaneous lymphoid proliferations, published data support a nonaggressive therapeutic strategy, particularly for patients presenting with solitary lesions.

Objective.To investigate a large outbreak of scabies in an intensive care unit of a university hospital and an affiliated rehabilitation center, and to establish effective control measures to prevent further transmission.Design.Outbreak investigation.Setting.The intensive care unit of a 750-bed university hospital and an affiliated 92-bed rehabilitation center.Methods.All exposed individuals were screened by a senior staff dermatologist. Scabies was diagnosed on the basis of (1) identification of mites by skin scraping, (2) identification of mites by dermoscopy, or (3) clinical examination of patients without history of prior treatment for typical burrows. During a follow-up period of 6 months, the attack rate was calculated as the number of symptomatic individuals divided by the total number of exposed individuals.Interventions.All exposed healthcare workers (HCWs) and their household members underwent preemptive treatment. Initially, the most effective registered drug in Switzerland (ie, topical lindane) was prescribed, but this prescribption was switched to topical permethrin or systemic ivermectin as a result of the progression of the outbreak. Individuals with any signs or symptoms of scabies underwent dermatological examination.Results.Within 7 months, 19 cases of scabies were diagnosed, 6 in children with a mean age of 3.1 years after exposure to the index patient with HIV and crusted scabies. A total of 1,640 exposed individuals underwent preemptive treatment. The highest attack rate of 26%–32% was observed among HCWs involved in the care of the index patient. A too-restricted definition of individuals at risk, non-compliance with treatment, and the limited effectiveness of lindane likely led to treatment failure, relapse, and reinfestation within families.Conclusions.Crusted scabies resulted in high attack rates among HCWs and household contacts. Timely institution of hygienic precautions with close monitoring and widespread, simultaneous scabicide treatment of all exposed individuals are essential for control of an outbreak.

Pachydermodactyly (PDD) is a benign, asymptomatic soft tissue swelling affecting the skin of the lateral aspects of the proximal interphalangeal joints of the fingers II-IV, mostly in young adolescent males, and could be interpreted as a consequence of tic-like behaviour as an obsessive-compulsive disorder in male adolescents. The differential diagnosis includes numerous diseases; a rapid clinical recognition of PDD would avoid many useless and expensive diagnostic tests. There is no effective medical treatment for PDD, but discontinuation of the tic-like mechanical traumatisation generally leads to a marked amelioration of the finger swelling. In this article we review the world literature, which contains 87 additional cases on this topic.

About 30% of dermatology patients have signs or symptoms of psychological problems. Dermatologists should be familiar with the basics needed to identify, advise and treat these patients. Because of the complex interaction between skin and psyche, it is difficult to distinguish whether the primary problem is the skin or the psyche. Sometimes the clinical picture is a consequence of interactions between them and other factors. The interactions between skin and psyche are well known in history, art and literature--perhaps better known today because the marked emphasis on such images in our modern multimedia society. Aging is increasingly perceived as an illness and not as a physiological process. Through globalization, many different cultural approaches to the skin have entered in our daily life and influence our communication. This article considers the most important dermatoses which often show primary or secondary interaction with the psyche.